Renin is an enzyme that participates in blood pressure regulation and contributes to the elevated blood pressure of many hypertensive patients. The objective of the proposed research is to study the physiological and biochemical characteristics of prorenin, an inactive form of renin in human plasma. We have shown that plasma prorenin can be converted to active renin following incubation with urinary kallikrein, plasma kallikrein or plasmin. Biochemical characterization of plasma prorenin will include partial purificaion, enzyme kinetic analysis, and investigation of the mechanisms whereby in vivo activation of plasma prorenin occurs. The research goals for the coming year include characterization of the interrelationships between prorenin, activating enzymes and competing substrates and inhibitors of the activating enzymes. Partial purification of plasma prorenin and amniotic fluid prorenin will be carried out, together with chromatographic characterization of the activating enzymes and inhibitors. A large scale purification of human renal renin will be started in order to prepare monospecific antibodies to human renal renin using the hybridoma technique.